In the past 5 years, continuous-flow (CF) rotary pumps have replaced volume-displacement pulsatile-flow pumps because of their simplicity, increased mechanical reliability, improved durability, smaller size, and better outcomes. In contrast to left ventricular assist devices (LVADs), existing clinical total artificial hearts (TAH) are all volume-displacement pulsatile-flow pumps, and they have significant limitations in their large size and durability. In response to these limitations, Cleveland Clinic has been developing a unique, valveless, and sensorless CFTAH with induced pulse under the current NIH-funded program (R01 HL096619). It has a single, continuously rotating, brushless DC motor and pump assembly with a centrifugal pump on both ends of the rotor. The pump passively balances left and right atrial pressures without sensors and is small enough (6.6 cm in diameter and 9.8 cm in length) to fit in small patients. The most recent, three consecutive calf experiments, conducted with no anticoagulation therapy, demonstrated outstanding biocompatibility with no thromboembolism in any organs. The animals remained healthy and were sacrificed at the planned duration of 30 or 90 days, which is the current world's record for longest duration of implant for a TAH with a single moving part. The objectives of this competitive renewal application are (1) to improve and refine the current CFTAH design by implementing the lessons learned from the prior program, (2) to develop a new continuous patient monitor (CPM) to enhance the real-time output of hemodynamic and pump information, and (3) to study the effects of pulsatility on pathophysiology with this ideal experimental platform. Specific aims to achieve these objectives are (1) Analyze the system requirements and refine the pump design, with input from clinical and industry experts and CFD analysis, to further improve biocompatibility, inherent hydraulic pump regulation, durability, and automatic flow control. (2) Develop and evaluate the real-time CPM using power and force- balanced rotor position signals to estimate pump flow, systemic and pulmonary pressure gradients and vascular resistances, inlet pressure difference, left and/or right suction and its severity, and blockage proximal to the pump, (3) Complete in vitro validation of system performance and level of hemolysis over the clinically relevant range of operation, (4) Complete in vivo animal experiments to validate hemodynamic response, biocompatibility, self-regulating mechanical design, and automatic speed control, and (5) Evaluate the effects of nonpulse or reduced pulse on hemodynamic response and pathophysiology with the same device by performing in vivo pulsatility studies. The successful completion of this program will demonstrate the safety and effectiveness of this CFTAH technology, making it ready for technology transfer, and ultimately providing clinicians with a valuable treatment option for patients with biventricular heart failure, which is the goal o this project.